PROJECT SUMMARY Over one in four Asian Americans who survive to age 65 can expect to be diagnosed with Alzheimer?s disease and related dementias (ADRD), yet Asian Americans are under-represented in ADRD research, and heterogeneity in risk across Asian ethnic groups is poorly understood. In the most comprehensive study to date, our research team discovered marked differences in ADRD incidence between Asian American ethnic groups (ADRD incidence was 27% higher in Filipino Americans than Chinese Americans). Despite the major differences in ADRD risk between groups, all Asian ethnic groups had lower ADRD risk than non-Latino whites (25% higher rate in non-Latino whites than Asian Americans). These findings have major public health implications: reducing ADRD rates in all racial/ethnic groups to rates observed in Asian Americans would prevent >190,000 ADRD cases annually in the U.S. Yet it is unknown why Asian Americans have lowered ADRD incidence or why Asian ethnic groups differ. Disentangling these puzzles will inform our understanding of the determinants of ADRD in people of all racial/ethnic backgrounds and help address the major gap in research on drivers of health in Asian Americans, the fastest growing racial/ethnic group in the U.S. The overall objective of this application is to examine how social factors, cardiometabolic health, and genetic factors contribute to lower ADRD risk in Asian Americans and differences in risk between Asian ethnic groups (Filipino Americans, Chinese Americans, and Japanese Americans). The rationale for the proposed research is that delineating risk and protective factors for ADRD in Asian Americans will unlock why Asian Americans have lower ADRD risk than other racial/ethnic groups and identify potential strategies to prevent ADRD and reduce ADRD disparities. We have assembled survey data, neighborhood information, and 24 years of medical records on ~12,000 Filipino, Japanese, and Chinese American Kaiser health plan members that will be matched 1:3 to a sample of non-Latino whites. Further, approximately 25% of the sample has genotype data available. This is the largest, most diverse longitudinal sample of Asian Americans with a rich set of biomedical and social data relevant to ADRD available. Our Specific Aims are: 1) evaluate the role of social factors (generational status, educational attainment, income, neighborhood disadvantage metrics, neighborhood ethnic enclaves) on ADRD risk in Asian Americans; 2) evaluate the role of cardiometabolic health (diabetes, hypertension, stroke) on ADRD risk in Asian Americans; 3) determine whether genetic ancestry and APOE genotype influence variation in ADRD incidence observed in Asian Americans. Examining the roles of social, cardiometabolic, and genetic factors on ADRD risk in a large, diverse cohort of Asian Americans and whites will provide valuable information to prevent ADRD in people of all racial/ethnic backgrounds and reduce ADRD disparities.